Dr. Lile's graduate and post-doctoral research focused on the neuropharmacological basis of stimulant addiction and how the neurotransmitter systems that mediate the effects of stimulants could be targeted for medications development. The career development and research plan proposed in this application outlines the training that will enable him to apply his previous experience, along with new methodolgies, to an emerging area of research, the treatment of cannabis-related disorders. Despite the fact that cannabis use is more prevalent than for any other illicit drug and can progress to abuse and dependence, there are no pharmacotherapies for these disorders and little clinical research has been conducted to this end. The experiments described here were designed to identify the neurotransmitter systems that are involved in the effects of the primary active constituent of cannabis, delta 9-THC, in humans. The primary outcome variable for these experiments is the interoceptive cue produced by delta 9-THC. The interoceptive effects of delta 9- THC will be measured using the drug-discrimination procedure, which is a pharmacologically specific and sensitive means to characterize the profile of a drug. Because cannabis-related disorders are associated with maladaptive changes in behavior and cognition, additional experimental measures to assess reinforcement, subjective ratings, impulsivity, psychomotor performance, learning and memory will also be taken. The role of the cannabinoid, opioid, GABA and dopamine systems will be investigated, which will reveal targets for future research efforts. Dr. Lile will be sponsored by Dr. Kelly, an expert in cannabis research in humans. The conduct of these experiments and the training described in this proposal will occur at the University of Kentucky, which has an extensive community of scientists engaged in basic and clinical research related to drug addiction. This award will allow Dr. Lile to develop as an independent investigator and to establish a program of human research concentrated on cannabis-related disorders.